Protein degradation and synthesis in the body are regulated by proteasome activity of multimeric protease complex. The protein conjugated to multiple units of polypeptide proteasome ubiquitin are degraded by proteasome. The accumulation of ubiquitinated proteins can lead to apoptosis. The proteasome units include 20S core catalytic complex and 19S regulatory subunits at each end, forming 26S complex. Ubiquitin is 76 amino acids complex and covalently linked to proteins by an enzymatic reaction.

According to the research findings, most of the drug candidates of the proteasome inhibitor therapeutics are being developed as the small molecules.

Majority of companies in the pipeline have innovated various advanced technologies for developing drug candidates as proteasome inhibitors. For instance, Ensemble Therapeutics’, Corporation technology platform is an efficient and productive approach for developing synthetic macrocycles and other less conventional small molecules. While macrocycles are a class of compounds that have traditionally been obtained from natural sources, the company is synthesizing successfully the synthetic macrocycles possessing drug-like properties and features. Using this approach, the company has developed a pipeline of proprietary and partnered programs that focus on both extracellular proteins (e.g. IL-17) and challenging intracellular targets (e.g. IAPs, IDO and USP9x).

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